Prodrugs and Drug Latentiation Flashcards Preview

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Flashcards in Prodrugs and Drug Latentiation Deck (20):
1

Prodrugs

Compounds that are initially inactive but later activated by either chemical or metabolic processes

2

Hard drug

Drug that has been designed to be resistant to metabolic events

3

Soft drug

Drug that has been designed to become metabolically inactivated after serving its purpose

4

2 routes by which prodrugs are activated in a physiological setting

1. Metabolic enzymes
2. Chemical transformations (hydrolysis, decarboxylation)

5

Carrier-linked prodrugs

Attached through a metabolically-labile linkage to another molecule (the promoiety)

6

Mutual prodrugs

Both the prodrug and the promoiety have activity

7

Bioprecursors

Prodrugs that rely on metabolism to introduce the functionality necessary for an active compound

8

Most common type of prodrug for carboxylic acids and alcohols

Esters

9

Esters that can be hard to hyrdrolyze by esterases and how this can be circumvented

Sterically-hindered esters can be hard to hydrolyze
Can sometimes be circumvented by using a double-ester

10

Why amides aren't good prodrugs for amines

Amides are fairly stable to chemical hydrolysis
Amidases aren't as common or promiscuous as esterases

11

Prodrugs of amines

Azo compounds (can be reduced to amines)

12

Prodrugs of carbonyl compounds

Aldehydes and ketones can be converted to acetal-like linkages with oxygen, nitrogen, and sulfur heteroatoms

13

Which is more common, oxidative or reductive activation of prodrugs?

Oxidative activation- high prevalence of cytochrome P 450s

14

Prodrug activation via phosphorylation

Commonly used by antiviral agents: disrupt synthesis and function of DNA/RNA

15

Activation via chemical processes

Can achieve selective activation based on the chemical environment of tissues (ex- drugs activated in acidic environment of stomach)
Tough to control: chemical reactions occur automatically

16

Advantages of prodrugs

Site-selective delivery of drug
Increase drug efficacy and reduce non-specific toxicity

17

Most common tissue-selective carrier promoiety that prodrugs can be coupled with

Antibodies

18

Tumor-activated prodrugs

Cancerous cells often exhibit increased activity for a number of metabolic enzymes, allowing certain anti-cancer agents to become selectively activated in tumor cells

19

Crossing the blood-brain barrier

CNS prodrugs need to be lipophilic: blood-brain barrier is lipophilic

20

Selective delivery to the GI tract

Colon has a variety of glucosidase enzymes found nowhere else in the human body
Glucoside-drug conjugates can be selectively unmasked in the colon